Although magnesium sulfate (MgSO4) is widely used as an analgesic adjuvant to peripheral analgesic cocktails, its efficacy in total knee arthroplasty (TKA) is still controversial. Therefore, we systematically reviewed and meta-analyzed the literature to assess the analgesic efficacy of MgSO4 as an adjuvant to the analgesic cocktail in TKA. The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched. The meta-analysis was performed according to the PRISMA guidelines. Data were qualitatively synthesized or meta-analyzed using a random-effects model. Five randomized controlled trials involving 432 patients were included. Meta-analyses detected significant differences between the MgSO4 and control groups in the visual analog scale (VAS) pain scores (rest) at 6, 12, and 24 h postoperatively; VAS pain scores (motion) at 12, 24, and 48 h postoperatively; morphine consumption within 24 h, 24-48 h, and during the total hospitalization period; time to first rescue analgesia after TKA; and length of hospital stay. Regarding the functional recovery, the meta-analysis demonstrated significant differences between groups in terms of knee range of motion on postoperative day 1; daily mobilization distance on postoperative day 1; and daily mobilization distance. There was no significant intergroup difference in surgical complications. The findings suggest that MgSO4 is a promising adjunct to the analgesic cocktail, achieving significant improvements in pain scores and total opioid consumption during the early postoperative period after TKA.